Isomer-dependent daunomycin release and in vitro antitumour effect of cis-aconityl-daunomycin

Judit Reményi, B. Balázs, S. Tóth, A. Falus, Gábor Tóth, F. Hudecz

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Two isomers of cis-aconytil-daunomycin (cAD) were isolated after the reaction of daunomycin with cis-aconitic-anhydride. The structure of the isomers was identified by MS-spectroscopy and 1H and 13C NMR experiments. In contrast with the assumptions described earlier, our results show that the two isomers belong to the cis- and trans-isomers of the α-monoamide of cis-aconityl-daunomycin, respectively. We found that the pH dependent daunomycin release is different for the two isomers. Comparative analysis of the in vitro antitumour effect of the isomers on c26 colon carcinoma and on MDA-MB 435P human breast carcinoma cell lines showed that cAD-1 is more potent than cAD-2, but the extent of differences is tumour cell dependent. The results of this study might be appreciated in the light of the use of acid-labile spacer for the design and preparation of protein/peptide conjugates of drugs by indicating that isomers could possess markedly different biological activity.

Original languageEnglish
Pages (from-to)556-561
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume303
Issue number2
DOIs
Publication statusPublished - Apr 4 2003

Fingerprint

Daunorubicin
Isomers
Cells
Spectrum Analysis
Colon
Bioactivity
N-aconityldaunomycin
In Vitro Techniques
Breast Neoplasms
Carcinoma
Cell Line
Peptides
Tumors
Acids
Nuclear magnetic resonance
Spectroscopy
Pharmaceutical Preparations
Neoplasms
Proteins

Keywords

  • cis-Aconytil-daunomycin isomers
  • Daunomycin
  • Isomer cytotoxicity
  • NMR structure identification
  • pH-dependent liberation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Isomer-dependent daunomycin release and in vitro antitumour effect of cis-aconityl-daunomycin. / Reményi, Judit; Balázs, B.; Tóth, S.; Falus, A.; Tóth, Gábor; Hudecz, F.

In: Biochemical and Biophysical Research Communications, Vol. 303, No. 2, 04.04.2003, p. 556-561.

Research output: Contribution to journalArticle

@article{45101dccd96345ba8bd07b8763d0734f,
title = "Isomer-dependent daunomycin release and in vitro antitumour effect of cis-aconityl-daunomycin",
abstract = "Two isomers of cis-aconytil-daunomycin (cAD) were isolated after the reaction of daunomycin with cis-aconitic-anhydride. The structure of the isomers was identified by MS-spectroscopy and 1H and 13C NMR experiments. In contrast with the assumptions described earlier, our results show that the two isomers belong to the cis- and trans-isomers of the α-monoamide of cis-aconityl-daunomycin, respectively. We found that the pH dependent daunomycin release is different for the two isomers. Comparative analysis of the in vitro antitumour effect of the isomers on c26 colon carcinoma and on MDA-MB 435P human breast carcinoma cell lines showed that cAD-1 is more potent than cAD-2, but the extent of differences is tumour cell dependent. The results of this study might be appreciated in the light of the use of acid-labile spacer for the design and preparation of protein/peptide conjugates of drugs by indicating that isomers could possess markedly different biological activity.",
keywords = "cis-Aconytil-daunomycin isomers, Daunomycin, Isomer cytotoxicity, NMR structure identification, pH-dependent liberation",
author = "Judit Rem{\'e}nyi and B. Bal{\'a}zs and S. T{\'o}th and A. Falus and G{\'a}bor T{\'o}th and F. Hudecz",
year = "2003",
month = "4",
day = "4",
doi = "10.1016/S0006-291X(03)00394-2",
language = "English",
volume = "303",
pages = "556--561",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Isomer-dependent daunomycin release and in vitro antitumour effect of cis-aconityl-daunomycin

AU - Reményi, Judit

AU - Balázs, B.

AU - Tóth, S.

AU - Falus, A.

AU - Tóth, Gábor

AU - Hudecz, F.

PY - 2003/4/4

Y1 - 2003/4/4

N2 - Two isomers of cis-aconytil-daunomycin (cAD) were isolated after the reaction of daunomycin with cis-aconitic-anhydride. The structure of the isomers was identified by MS-spectroscopy and 1H and 13C NMR experiments. In contrast with the assumptions described earlier, our results show that the two isomers belong to the cis- and trans-isomers of the α-monoamide of cis-aconityl-daunomycin, respectively. We found that the pH dependent daunomycin release is different for the two isomers. Comparative analysis of the in vitro antitumour effect of the isomers on c26 colon carcinoma and on MDA-MB 435P human breast carcinoma cell lines showed that cAD-1 is more potent than cAD-2, but the extent of differences is tumour cell dependent. The results of this study might be appreciated in the light of the use of acid-labile spacer for the design and preparation of protein/peptide conjugates of drugs by indicating that isomers could possess markedly different biological activity.

AB - Two isomers of cis-aconytil-daunomycin (cAD) were isolated after the reaction of daunomycin with cis-aconitic-anhydride. The structure of the isomers was identified by MS-spectroscopy and 1H and 13C NMR experiments. In contrast with the assumptions described earlier, our results show that the two isomers belong to the cis- and trans-isomers of the α-monoamide of cis-aconityl-daunomycin, respectively. We found that the pH dependent daunomycin release is different for the two isomers. Comparative analysis of the in vitro antitumour effect of the isomers on c26 colon carcinoma and on MDA-MB 435P human breast carcinoma cell lines showed that cAD-1 is more potent than cAD-2, but the extent of differences is tumour cell dependent. The results of this study might be appreciated in the light of the use of acid-labile spacer for the design and preparation of protein/peptide conjugates of drugs by indicating that isomers could possess markedly different biological activity.

KW - cis-Aconytil-daunomycin isomers

KW - Daunomycin

KW - Isomer cytotoxicity

KW - NMR structure identification

KW - pH-dependent liberation

UR - http://www.scopus.com/inward/record.url?scp=0347296265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347296265&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)00394-2

DO - 10.1016/S0006-291X(03)00394-2

M3 - Article

C2 - 12659854

AN - SCOPUS:0347296265

VL - 303

SP - 556

EP - 561

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -